Palbociclib - from Bench to Bedside and Beyond

Endocrine therapy is the cornerstone in the treatment of hormone receptor-positive breast cancer. During the last decades, much has been learned about the subtle regulation of the cell cycle. In this tightly regulated network, cyclin-dependent kinases (CDKs) play a pivotal role. Especially CDK4/6 is the key regulator of the G1-S transition. Realizing its importance, specific inhibitors of CDK4/6 were developed. The drug most advanced in clinical development in this class is palbociclib (PD 0332991). This review highlights preclinical data and brings into focus early clinical trials that led to an accelerated approval by the US Food and Drug Administration (FDA) as first-line treatment in combination with letrozole in advanced hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Furthermore, ongoing clinical trials with palbociclib in advanced and in early breast cancer are outlined. In conclusion, inhibition of CDK4/6 using palbociclib in combination with endocrine therapy is an efficacious treatment option in hormone receptor-positive/HER2-negative advanced breast cancer. Ongoing clinical trials will show whether palbociclib is ready for prime time in early breast cancer.